Embolic strokes of undetermined source in young adults: baseline characteristics and long-term outcome.

BACKGROUND AND PURPOSE: Embolic strokes of undetermined source (ESUS) are a recent entity, not yet thoroughly investigated in young stroke patients. The clinical characteristics and long-term risks of vascular events and all-cause mortality between young-onset ESUS and other aetiological subgroups were compared. METHODS: Patients with ESUS were identified amongst the 1008 patients aged 15-49 years with first-ever ischaemic stroke in Helsinki Young Stroke Registry, and primary end-points were defined as recurrent stroke, composite vascular events and all-cause mortality. Cumulative 15-year risks for each end-point were analysed with life tables and adjusted risks were based on Cox proportional hazard analyses. RESULTS: Of the 971 eligible patients, 203 (20.9%) were classified as ESUS. They were younger (median age 40 years, interquartile range 32-46 vs. 45 years, 39-47), more often female (43.3% vs. 35.7%) and had fewer cardiovascular risk factors than other modified TOAST groups. With a median follow-up time of 10.1 years, ESUS patients had the second lowest cumulative risk of recurrent stroke and composite vascular events and lowest mortality compared to other TOAST groups. Large-artery atherosclerosis and small vessel disease carried significantly higher risk for recurrent stroke than did ESUS, whilst no difference appeared between cardioembolism from high-risk sources and ESUS. CONCLUSIONS: In our cohort, ESUS patients were younger and had milder cardiovascular risk factor burden and generally better long-term outcome compared to other causes of young-onset stroke. The comparable risk of recurrent stroke between ESUS and high-risk sources of cardioembolism might suggest similarities in their pathophysiology.

Raccoon dog model shows preservation of bone during prolonged catabolism and reduced physical activity.

The raccoon dog (Nyctereutes procyonoides) is a promising animal model capable of preventing disuse-induced osteoporosis. Previous data suggest that this species resembles bears in the preservation of bone mass and biomechanical properties during prolonged passivity and catabolism. This longitudinal study examined the osteological properties of tibiae in farm-bred raccoon dogs that were either fed or fasted (n=6 per group) for a 10 week period. Peripheral quantitative computed tomography was utilized and plasma markers of bone turnover measured before fasting and at 9 weeks followed by mechanical testing (three-point bending), micro-computed tomography and Fourier transform infrared imaging at 10 weeks. Passive wintering with prolonged catabolism (body mass loss 32%) had no significant effects on bone mineralization, porosity or strength. The concentration of C-terminal telopeptide of type I collagen, indicative of bone resorption, increased in the plasma of the fasted raccoon dogs, while the bone formation markers were unchanged. The levels of 25-hydroxyvitamin D were reduced in the fasted animals. Based on these data, the preservation of bone in wintering raccoon dogs shares characteristics with that of bears with no apparent decrease in the formation of bone but increased resorption. To conclude, raccoon dogs were able to minimize bone loss during a 10 week period of catabolism and passivity.

Cooper pair splitting by means of graphene quantum dots.

A split Cooper pair is a natural source for entangled electrons which is a basic ingredient for quantum information in the solid state. We report an experiment on a superconductor-graphene double quantum dot (QD) system, in which we observe Cooper pair splitting (CPS) up to a CPS efficiency of ∼10%. With bias on both QDs, we are able to detect a positive conductance correlation across the two distinctly decoupled QDs. Furthermore, with bias only on one QD, CPS and elastic cotunneling can be distinguished by tuning the energy levels of the QDs to be asymmetric or symmetric with respect to the Fermi level in the superconductor.

Packaging gas selects lactic acid bacterial communities on raw pork.

AIMS: To study the effect of different CO2-rich packaging atmospheres on the composition of lactic acid bacterial communities proliferating on raw pork. METHODS AND RESULTS: Raw pork loin was inoculated with a mixture of 14 lactic acid bacteria (LAB) strains previously associated with meat and packaged with four gas atmospheres: (i) 100% CO2 (ii) 80% N2 20% CO2 (iii) 80% N2, 20% CO2, 0·4% CO and (iv) 80% O2, 20% CO2. The colony counts of LAB, pH and composition of packaging gas were monitored every other day during the storage of 14 days at +6°C. The compositions of lactic acid bacterial communities on pork were evaluated after 7 days of storage with culture-independent, terminal restriction fragment length polymorphism analysis of 16S rRNA gene fragments. After 14 days of storage, the compositions of lactic acid bacterial communities were evaluated using identification of plate-grown LAB isolates by numerical ribopattern analysis. The results showed that (i) high concentration of CO2 in packaging atmosphere favoured Lactobacillus sp. (ii) high concentration of O2 favoured Leuconostoc spp. (iii) atmosphere with 80% N2, 20% CO2 favoured Lactococcus sp. CONCLUSIONS: The composition of modified packaging atmosphere is a major factor selecting lactic acid bacterial communities proliferating on raw meat. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides an explanation for the compositions of lactic bacterial communities on modified atmosphere packaged raw meat observed in other studies. The results should be considered when attempting to manipulate LAB communities in raw meat, e.g. by protective cultures.

Phase-transition-like properties of double-beam optical tweezers.

We report on double-beam optical tweezers that undergo previously unknown phase-transition-like behavior resulting in the formation of more optical traps than the number of beams used to create them. We classify the optical force fields which produce multiple traps for a double-beam system including the critical behavior. This effect is demonstrated experimentally in orthogonally polarized (noninterfering) dual-beam optical tweezers for a silica particle of 2.32 µm diameter. Phase transitions of multiple beam trapping systems have implications for hopping rates between traps and detection of forces between biomolecules using dual-beam optical tweezers. It is an example of a novel dynamic system with multiple states where force fields undergo a series of sign inversions as a function of parameters such as size and beam separation.

Comment on: "A novel approach to peatlands as archives of total cumulative spatial pollution loads from atmospheric deposition of airborne elements complementary to EMEP data: Priority pollutants (Pb, Cd, Hg)" by Ewa Miszczak, Sebastian Stefaniak, Adam Michczynski, Eiliv Steinnes and Irena Twardowska.

A recent paper by Miszczak et al. (2020) examines metal contamination of mires in Poland and Norway. The authors conclude that lead (Pb) records in ombrotrophic peatlands cannot be used to reconstruct the chronological history of anthropogenic activities due to post-depositional mobility of the metal. We contest this general conclusion which stands in contrast with a significant body of literature demonstrating that Pb is largely immobile in the vast majority of ombrotrophic peatlands. Our aim is to reaffirm the crucial contribution that peat records have made to our knowledge of atmospheric Pb contamination. In addition, we reiterate the necessity of following established protocols to produce reliable records of anthropogenic Pb contamination in environmental archives.

Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors.

Hereditary non-polyposis colorectal carcinoma (Lynch syndrome) is among the most common hereditary cancers in man and a model of cancers arising through deficient DNA mismatch repair (MMR). Lynch syndrome patients are predisposed to different cancers in a non-random fashion, the basis of which is poorly understood. We addressed this issue by determining the molecular profiles for different tumors from a nationwide cohort of Lynch syndrome families (approximately 150 tumors in total). We focused on some less prevalent cancers, affecting the brain (n = 7) and urinary tract (five bladder and five ureter uroepithelial cancers and four kidney adenocarcinomas), and compared their molecular characteristics to those of the most common cancers, colorectal, gastric and endometrial adenocarcinomas, from the same families. Despite origin from verified MMR gene mutation carriers, the frequency of high-level microsatellite instability in tumors varied between high (100-96% for ureter, stomach and colon), intermediate (63-60% for endometrium and bladder) and low (25-0% for kidney and brain). In contrast to gastrointestinal and endometrial carcinomas, active (nuclear) beta-catenin was rare and KRAS mutations were absent in brain and urological tumors. Compared with other tumors, frequent stabilization of p53 protein characterized urinary tract cancers. Promoter methylation of tumor suppressor genes discriminated the tumors in an organ-specific manner. Our findings suggest that different Lynch syndrome tumors develop along different routes. Uroepithelial cancers of the ureter (and bladder to lesser extent) share many characteristics of MMR deficiency-driven tumorigenesis, whereas brain tumors and kidney adenocarcinomas follow separate pathways.

The prognostic value of haemodynamic parameters in the recovery phase of an exercise test. The Finnish Cardiovascular Study.

We tested the hypothesis that the change from the peak to recovery values of systolic arterial pressure (SAP recovery) and rate-pressure product (RPP recovery) can be used to predict all-cause and cardiovascular mortality, as well as sudden cardiac death (SCD) in patients referred to a clinical exercise stress test. As a part of the Finnish Cardiovascular Study (FINCAVAS), consecutive patients (n=2029; mean age+/-SD=57+/-13 years; 1290 men and 739 women) with a clinically indicated exercise test using a bicycle ergometer were included in the present study. Capacities of attenuated SAP recovery, RPP recovery and heart rate recovery (HRR) to stratify the risk of death were estimated. During a follow-up (mean+/-s.d.) of 47+/-13 months, 122 patients died; 58 of the deaths were cardiovascular and 33 were SCD. In Cox regression analysis after adjustment for the peak level of the variable under assessment, age, sex, use of beta-blockers, previous myocardial infarction and other common coronary risk factors, the hazard ratio of the continuous variable RPP recovery (in units 1000 mm Hg x b.p.m.) was 0.85 (95% CI: 0.73-0.98) for SCD, 0.87 (0.78-0.97) for cardiovascular mortality, and 0.87 (0.81 to 0.94) for all-cause mortality. SAP recovery was not a predictor of mortality. The relative risks of having HRR below 18 b.p.m., a widely used cutoff point, were as follows: for SCD 1.28 (0.59-2.81, ns), for cardiovascular mortality 2.39 (1.34-4.26) and for all-cause mortality 2.40 (1.61-3.58). In conclusion, as a readily available parameter, RPP recovery is a promising candidate for a prognostic marker.

The influence of hemodynamic factors on left ventricular mass.

We evaluated the relationship between the variability in the left ventricular mass index (LVMI) and different hemodynamic factors. LVMI was associated with blood pressure and, in one subgroup, strongly to arterial pulse wave velocity (PWV). High physical activity was connected to increased LVMI, and a combination of low stroke index (SI) and high heart rate (HR) to decreased LVMI.

Proliferation of mycobacteria in a piggery environment revealed by mycobacterium-specific real-time quantitative PCR and 16S rRNA sandwich hybridization.

Pig mycobacteriosis is the most common animal mycobacterial disease in Finland with a long-term average prevalence of 0.34% and temporary peaks as high as 0.85%. In the current study Mycobacterium-specific real-time qPCR and 16S rRNA sandwich hybridization were utilized for culture-independent detection and measurement of potentially infectious mycobacteria in selected piggeries. Participating herds (n=5) were selected according to prevalence of tuberculous lesions (>4%) in slaughtered carcasses. When DNA extracted from piggery bedding materials was analyzed by Mycobacterium-targeted qPCR using the SYBR green I dye for detection of amplification products, 10(5) to 10(7) cell equivalents of mycobacterial DNA were detected in unused bedding materials and 10(8) to 10(10)g(-1) dry weight in used bedding materials. When Mycobacterium-specific hybridization probes were used for detection of amplification products, 10(5) to 10(7) cell equivalents of mycobacterial DNA g(-1) dry weight were detected in unused bedding materials in four out of the five piggeries studied and up to 10(8) cell equivalents in used bedding material. The results were confirmed by the Mycobacterium-specific 16S rRNA sandwich hybridization assay. The present results show, that mycobacteria occur in organic materials commonly used on pig farms, and may proliferate in bedding materials during use. We also show that DNA- and RNA-based methods may be utilized for detection of environmental reservoirs of mycobacteria causing porcine and human infection.

Toxinogenic Bacillus pumilus and Bacillus licheniformis from mastitic milk.

To elucidate the occurrence of heat-stable toxin-producing strains among mastitic Bacillus isolates, 100 milk samples of mastitic cows from different parts of Finland were screened. Bacillus was identified as the major organism in 23 samples. Toxinogenic Bacillus isolates identified by sperm cell motility inhibition assay were isolated from six samples. Four isolates belonged to the species Bacillus pumilus and two to Bacillus licheniformis. The toxic substances were heat-stable and soluble to methanol thus being of non-protein nature. The methanol extracted substances disrupted the sperm cell plasma membrane permeability barrier at exposure concentrations of 1-15 microg ml(-1) (B. pumilus) or 20-30 microg ml(-1) (B. licheniformis). The toxic properties of the two mastitic B. licheniformis strains were similar to those of B. licheniformis strains known to produce the lipopeptide lichenysin A and the synthetase genes lchAA, lchAB and lchAC for lichenysin were found in the mastitic strains by PCR. Toxin synthetase genes for the syntheses of lichenysin or surfactin were searched but not found in the toxic B. pumilus strains. The ribopatterns of the mastitic B. pumilus and B. licheniformis isolates were similar to those of the toxinogenic strains described earlier from food poisoning incidents and contaminated indoor air. B. licheniformis and B. pumilus survive pasteurization and other heat treatments as spores. Toxin-producing strains of these species in the dairy production chain may thus be of food safety concern.

Pulse wave velocity reference values in healthy adults aged 26-75 years.

The stiffening of arteries is associated with various cardiovascular diseases. Arterial stiffening can be studied utilizing arterial pulse wave velocity (PWV), but the absence of reliable reference values for PWV has limited its use in clinical practice. The aim of this study was to establish a range of reference values for PWV. PWV was examined by measuring the time difference of systolic pulse waves in arteries from the aortic arch to the popliteal artery using whole-body impedance cardiography (ICG). The study population consisted of 799 individuals (age range 25-76 years), 283 of whom had no evidence of cardiovascular disease, and a low burden of risk factors was selected to represent an apparently healthy population. In healthy study population, PWV was higher in males (8 x 9 +/- 1 x 8 m s(-1)) than females (8 x 1 +/- 2 x 0 m s(-1), P<0 x 001). Young males had lower PWV values than old males. Correspondingly, young females also had lower PWV values than old females. PWV was clearly associated with age, and PWV was higher in young and middle-aged males than in females. There was no statistically significant difference between old males and females in PWV. In conclusion, whole-body ICG provides a practical method for PWV measurement. Reference values can be useful in the clinical management of patients, especially in detecting early vascular disease or an increased risk of cardiovascular complications.

Remediation of heavy metal-contaminated forest soil using recycled organic matter and native woody plants.

The main aim of this study was to determine how the application of a mulch cover (a mixture of household biocompost and woodchips) onto heavy metal-polluted forest soil affects (i) long-term survival and growth of planted dwarf shrubs and tree seedlings and (ii) natural revegetation. Native woody plants (Pinus sylvestris, Betula pubescens, Empetrum nigrum, and Arctostaphylos uva-ursi) were planted in mulch pockets on mulch-covered and uncovered plots in summer 1996 in a highly polluted Scots pine stand in southwest Finland. Spreading a mulch layer on the soil surface was essential for the recolonization of natural vegetation and increased dwarf shrub survival, partly through protection against drought. Despite initial mortality, transplant establishment was relatively successful during the following 10 yr. Tree species had higher survival rates, but the dwarf shrubs covered a larger area of the soil surface during the experiment. Especially E. nigrum and P. sylvestris proved to be suitable for revegetating heavy metal-polluted and degraded forests. Natural recolonization of pioneer species (e.g., Epilobium angustifolium, Taraxacum coll., and grasses) and tree seedlings (P. sylvestris, Betula sp., and Salix sp.) was strongly enhanced on the mulched plots, whereas there was no natural vegetation on the untreated plots. These results indicate that a heavy metal-polluted site can be ecologically remediated without having to remove the soil. Household compost and woodchips are low-cost mulching materials that are suitable for restoring heavy metal-polluted soil.

Replacing risk-based early-onset-disease prevention with intrapartum group B streptococcus PCR testing.

OBJECTIVE: To evaluate the effect of a rapid PCR-based group B streptococcus (GBS) test on length of stay in hospital among newborns, antibiotic use, and GBS-early-onset-disease (EOD) incidence. METHODS: We conducted a before and after service evaluation including term deliveries between 1st January and 12th November 2014 (6688 deliveries). Length of stay in the hospital, GBS-EOD incidence and antibiotic use were evaluated. RESULTS: We recorded three confirmed and 74 possible cases of GBS-EOD in Phase 1, and 85 possible cases in Phase 2. In newborns with suspected infection, the introduction of the rapid test was related to a decreased length of stay on the pediatric care unit by 1.16 days (p = 0.01), and an increase in the length of stay on the mother-and-baby ward by 1.11 days (p < 0.001). No increase in antibiotics was noted. CONCLUSION: The introduction of a point of care test was associated with a reduction in length of stay in the pediatric care unit, without an increase in antibiotic use. This test could improve the accuracy of GBS colonization detection, and help to prevent intrapartum transmission as no verified GBS-EOD cases were recorded with the intrapartum PCR algorithm.

In vivo and in vitro degradation of a novel bioactive guided tissue regeneration membrane.

The aim of this study was to assess degradation of a novel bioactive guided tissue regeneration (GTR) membrane and to quantify the concurrent tissue responses. Pieces of membrane composed of poly-l-lactide, poly-d,l-lactide, trimethylenecarbonate and polyglycolide were dipped into an N-methyl-2-pyrroline (NMP) solution and implanted in the mandibles of 10 sheep. The animals were sacrificed at 6-104 weeks. Parallel in vitro degradation was analysed by measuring the inherent viscosity, water absorption and remaining mass. One of the 2 in vitro sets of membranes was prehandled with NMP. At 6-26 weeks in vivo, the gradually more degraded implants were surrounded by a fibrous network. At 52 and 104 weeks, the implants and fibrous networks were non-detectable. Foreign body granulomatous reactions were not observed. In vitro, the mass of the NMP-exposed membranes diminished linearly over the 2-year period down to 10%, while the non-NMP-exposed membrane maintained all their mass for the first 16 weeks. The membranes without NMP had absorbed significantly less water at weeks 4 and 8 than the other group. The inherent viscosity decreased relatively uniformly in the in vitro groups. In conclusion, the in vivo degradation was complete in 12 months with only mild histologic responses; the degradation in vitro may be slower. NMP accelerates the degradation.

Pneumococcal conjugate vaccination in toddlers: mucosal antibody response measured as circulating antibody-secreting cells and as salivary antibodies.

BACKGROUND: Our previous studies have shown an antibody-secreting cell (ASC) response to pneumococcal vaccines in adults and suggested that a high IgA ASC response is an indicator of a secretory IgA response in saliva. We believe that the mucosal immune response is potentially an important characteristic of the pneumococcal vaccines and should thus be measured when the new pneumococcal conjugate vaccines are evaluated. OBJECTIVES: To study mucosal and serum antibody responses to pneumococcal conjugate vaccines in toddlers. METHODS: Each investigational vaccine, containing either 3 or 10 microg of pneumococcal PS serotypes 6B, 14, 19F and 23F conjugated to either diphtheria toxoid (PncD) or tetanus protein (PncT), was administered to 10 children (a total of 40 children). The ASC response was measured on Day 7 after immunization by enzyme-linked immunospot assay, and the salivary and serum antibodies were measured before and 7 and 28 days after the immunization by enzyme immunoassay. RESULTS: The vaccines studied induced ASC responses to the pneumococcal polysaccharides (PS) in all children vaccinated. The ASC responses to the PS components of the vaccine (the geometric mean number of ASCs varying from 120 to 160 ASC/10(6) cells) were lower than those seen earlier in adults after conjugate vaccine (240 to 2015 ASC/10(6) cells), but comparable with those seen earlier in adults after pneumococcal PS vaccine (113 to 136 ASC/10(6) cells). The ASC response was clearly dominated by IgA-secreting cells. Salivary IgA responses were detected in 35% of the children, but IgG was rarely detected in saliva. A positive correlation was demonstrated between the number of IgA ASCs and salivary IgA concentration (r = 0.70, P = 0.01), suggesting that a high number of IgA ASCs after parenteral immunization is an indicator of a secretory IgA response in saliva. On Day 28 after immunization increased serum concentrations of IgG were detected in most vaccinees (75 to 95%, depending on the serotype). CONCLUSIONS: Both mucosal and systemic antibody responses were induced by PncD and PncT vaccines in toddlers.

Heart-rate variability and SIDS. Examination of heart-rate patterns using an expert system generator.

In a prospective, population-based study, HRV was analyzed from 24-hr tape recordings made on 16 full-term and one preterm infant who had subsequently suffered SIDS and compared to similar data on 23 control infants (n of recordings, 44). In the SIDS group, heart rate was higher, and overall and beat-to-beat HRV (CV, CVS, respectively) were lower, than in the controls, but not significantly. Respiratory rate and respiratory HRV (by spectral analysis) were similar in both groups. Assuming that cardiorespiratory mechanisms of SIDS are multifactorial, we expected that several subgroups would be detected in both test groups. Therefore, the average data for each recording were subsequently examined by means of an expert system generator (ExTran, Intelligent Terminals Ltd., Edinburgh, UK). By rules induced with 25 nodes, the following results were obtained: 16/44 recordings were diagnosed as SIDS on the basis of (1) respiratory rate (RR) less than 33 and CV less than 3.46% (n = 8); (2) RR greater than 33, CVS less than 2.18%, and BW greater than 3,520 g (n = 4); and (3) RR greater than 33, CVS less than 2.18%, BW less than 3,520 g, HR greater than 136, and CV greater than 1.89% (n = 4). Seventeen of 44 were considered as non-SIDS when (1) RR was 33-47.4, CVS greater than 2.18%, and RSA less than 74.3 and (2) RR greater than 33, CVS less than 2.18%, BW less than 3,520 g, and HR less than 142. The remaining 11 cases required more complicated rules in order to be classified. This study shows that although the trend of increased HR and decreased HRV in the SIDS cases was statistically non-significant, an expert system program may be helpful in defining decision rules to identify cases of SIDS on the basis of cardiorespiratory data.

Interactions between precipitation and Scots pine canopies along a heavy-metal pollution gradient.

Bulk precipitation and stand throughfall were collected during 1992-96 at distances of 0.5, 4 and 8 km from the Harjavalta Cu-Ni smelter, southwestern Finland. The amounts of heavy metals (Cu, Ni, Zn, Fe) and mineral nutrients in bulk precipitation and throughfall were highest at 0.5 km. Although the canopy coverage was low at 0.5 km, the amounts of heavy metals intercepted by the canopy were extremely high. The proportion of foliar leaching relative to the wash-off of dry deposition from the needle surfaces decreased on moving towards the smelter for all elements, except for K. The high rate of K leaching from the needle tissues close to the smelter demonstrated that the K throughfall flux has been greatly altered by the heavy pollution load.

Enrichment of Cu, Ni, Zn, Pb and As in an ombrotrophic peat bog near a Cu-Ni smelter in southwest Finland.

The accumulation of selected trace elements (Cu, Ni, Zn, Pb, As) in the surface peat layer of an ombrotrophic bog 2.4 km from a Cu-Ni smelter at Harjavalta, Finland was studied using a peat core. A reference core was taken from an ombrotrophic bog at a background site, Hietajärvi, in eastern Finland. Element concentrations were analysed from 1-cm slices and enrichment factors (EF) were calculated. The enrichment factors of both Cu and Ni in the Harjavalta peat bog are extremely high compared to the Hietajärvi site. However, only the 6-cm surface peat Pb values are higher in Harjavalta compared to Hietajärvi. Precipitation was collected during 1992-1996, in the vicinity of the Harjavalta smelter, in order to estimate the current atmospheric deposition load. Comparison between the precipitation and peat data reveals that at Harjavalta the surface peat is relatively much more polluted than the current precipitation. The variation in EF of the Harjavalta peat core with respect to depth shows two patterns: Cu and Pb are similar, as are Ni, Zn and As. The vertical gradient in Harjavalta Cu EF suggests that Cu supplied to the peat by atmospheric deposition is very well preserved by the bog.